Studies on the use of peptide auxiliaries in the meso-desymmetrization of epoxides, and the kinetic resolution of secondary alcohols

 

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dc.contributor.advisor Hunter, Roger en_ZA
dc.contributor.author Cozett, Rudy Edgar en_ZA
dc.date.accessioned 2016-01-26T12:06:47Z
dc.date.available 2016-01-26T12:06:47Z
dc.date.issued 2015 en_ZA
dc.identifier.citation Cozett, R. 2015. Studies on the use of peptide auxiliaries in the meso-desymmetrization of epoxides, and the kinetic resolution of secondary alcohols. University of Cape Town. en_ZA
dc.identifier.uri http://hdl.handle.net/11427/16573
dc.description Includes bibliographical references en_ZA
dc.description.abstract This thesis reports on the use of amino acids and peptides as chiral ligands/catalysts in two asymmetric processes: Meso-desymmetrization of an epoxide and the kinetic resolution of secondary alcohols. Chapter 1 comprises a literature review, which gives a general overview of methods of asymmetric synthesis, followed by an overview on the existing classes of asymmetric DMAP-type acyl-transfer catalysis as the major topic of the thesis. Chapter 2 describes the synthesis and evaluation of four peptide ligands used in combination with scandium(III) triflate for the meso-desymmetrization of cyclohexene oxide. Enantioselectivities were determined by chiral HPLC, and gave results of up to 41 % ee. Chapter 3 discusses the synthesis and characterisation of three clas ses of nucleophilic DMAP-type catalysts, in which various amino acid/peptide auxiliaries were attached either α, β, or γ-to the pyridine nitrogen. The peptides contained tryptophan, chosen to exploit a potential π - π stacking interaction with the acyl-pyridinium cation. Catalysts substituted at the α and γ positions gave no kinetic resolution for 1-(2-naphthyl)ethanol 121 ; however, a dipeptide (Leu-Trp)-containing catalyst 128 substituted at the β-position gave an s-v alue of 5.3. In order to improve the selectivity, 128 was derivatised at the C-terminal to form two tripeptide-containing catalysts, and acylated at the NH group of the indole ring (141). A range of secondary alcohols were tested and selectivity factors in creased to up to 10.7 . A series of second-generation catalysts were synthesised, but s-values did not improve. An NMR study was performed to reveal a possible conformational change during the stereoselective step. Computational modelling was performed using molecular mechanics (MMFF94) and quantum mechanics (B3LYP/6-31G, M06/6-31G*, ω B97X-D/6-31G) to determine a po ssible transition-state model, which indicated a π - cation interaction of the electron-rich indole ring of a tryptophan moiety with the electron-deficient pyridinium cation as a likely determinant of stereoselectivity. en_ZA
dc.language.iso eng en_ZA
dc.subject.other Chemistry en_ZA
dc.title Studies on the use of peptide auxiliaries in the meso-desymmetrization of epoxides, and the kinetic resolution of secondary alcohols en_ZA
dc.type Doctoral Thesis
uct.type.publication Research en_ZA
uct.type.resource Thesis en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Science en_ZA
dc.publisher.department Department of Chemistry en_ZA
dc.type.qualificationlevel Doctoral
dc.type.qualificationname PhD en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Cozett, R. E. (2015). <i>Studies on the use of peptide auxiliaries in the meso-desymmetrization of epoxides, and the kinetic resolution of secondary alcohols</i>. (Thesis). University of Cape Town ,Faculty of Science ,Department of Chemistry. Retrieved from http://hdl.handle.net/11427/16573 en_ZA
dc.identifier.chicagocitation Cozett, Rudy Edgar. <i>"Studies on the use of peptide auxiliaries in the meso-desymmetrization of epoxides, and the kinetic resolution of secondary alcohols."</i> Thesis., University of Cape Town ,Faculty of Science ,Department of Chemistry, 2015. http://hdl.handle.net/11427/16573 en_ZA
dc.identifier.vancouvercitation Cozett RE. Studies on the use of peptide auxiliaries in the meso-desymmetrization of epoxides, and the kinetic resolution of secondary alcohols. [Thesis]. University of Cape Town ,Faculty of Science ,Department of Chemistry, 2015 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/16573 en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Cozett, Rudy Edgar AB - This thesis reports on the use of amino acids and peptides as chiral ligands/catalysts in two asymmetric processes: Meso-desymmetrization of an epoxide and the kinetic resolution of secondary alcohols. Chapter 1 comprises a literature review, which gives a general overview of methods of asymmetric synthesis, followed by an overview on the existing classes of asymmetric DMAP-type acyl-transfer catalysis as the major topic of the thesis. Chapter 2 describes the synthesis and evaluation of four peptide ligands used in combination with scandium(III) triflate for the meso-desymmetrization of cyclohexene oxide. Enantioselectivities were determined by chiral HPLC, and gave results of up to 41 % ee. Chapter 3 discusses the synthesis and characterisation of three clas ses of nucleophilic DMAP-type catalysts, in which various amino acid/peptide auxiliaries were attached either α, β, or γ-to the pyridine nitrogen. The peptides contained tryptophan, chosen to exploit a potential π - π stacking interaction with the acyl-pyridinium cation. Catalysts substituted at the α and γ positions gave no kinetic resolution for 1-(2-naphthyl)ethanol 121 ; however, a dipeptide (Leu-Trp)-containing catalyst 128 substituted at the β-position gave an s-v alue of 5.3. In order to improve the selectivity, 128 was derivatised at the C-terminal to form two tripeptide-containing catalysts, and acylated at the NH group of the indole ring (141). A range of secondary alcohols were tested and selectivity factors in creased to up to 10.7 . A series of second-generation catalysts were synthesised, but s-values did not improve. An NMR study was performed to reveal a possible conformational change during the stereoselective step. Computational modelling was performed using molecular mechanics (MMFF94) and quantum mechanics (B3LYP/6-31G, M06/6-31G*, ω B97X-D/6-31G) to determine a po ssible transition-state model, which indicated a π - cation interaction of the electron-rich indole ring of a tryptophan moiety with the electron-deficient pyridinium cation as a likely determinant of stereoselectivity. DA - 2015 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2015 T1 - Studies on the use of peptide auxiliaries in the meso-desymmetrization of epoxides, and the kinetic resolution of secondary alcohols TI - Studies on the use of peptide auxiliaries in the meso-desymmetrization of epoxides, and the kinetic resolution of secondary alcohols UR - http://hdl.handle.net/11427/16573 ER - en_ZA


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